Home
Home

7th Call - Dr. Michael Fokuo Ofori

Project Title: Studies on the Roles of 5-Ht Receptor Subtypes in the Sporogonic Life Cycle of Plasmodium falciparum.

Principal Investigator: Dr. Michael Fokuo Ofori (Department of Immunology, NMIMR University of Ghana)

Email Address: mofori@noguchi.ug.edu.gh

Award Amount: GHC 24,995.00

Project Status: On-going

Summary:

Serotonin (5-hydroxytrptamine; 5-HT), a monoamine and a structural analogue of xanthurenic acid, belongs to a class of primitive neurotransmitters known as biogenic amines. These biogenic amines and their receptors play important biological roles in a diverse range of organisms ranging from the single-celled eukaryotes Paramecium and Tetrahymena to the multicellular Drosophila melanogaster. Serotonin has been found to regulate physiological functions of sleep and memory in the Drosophila melanogaster, motility and growth in Paramecium and its levels are lowered when mosquitoes feed and thereafter builds up to a threshold by the time of the next blood meal.

Serotonin has also been implicated in Ca2+ mobilization by Plasmodium parasites. Xanthurenic acid in the midgut of mosquito on the other hand has been identified as the gametocyte activating factor (GAF) that induces exflagellation of the parasite. These two biogenic monoamines are all by- products of tryptophan metabolism. In view of the ubiquitous nature of serotonin it is hypothesised that it plays an important role in the transmission and development of the gametocytes, which will be elucidated if gametocytes are cultured in the presence of antagonists to putative receptors of serotonin. This study will involve in vitro cultivation of malaria parasites for the generation of stage five gametocytes. Also,exflagellation assays will be used to test the effects of chemical antagonists on gametocyte development in vitro and also to determine the effective dose of any 5-HT receptor antagonist found to inhibit gametocyte development. It is expected that the 5-HT receptor antagonist would significantly disrupt the sporogonic development of P. falciparum. The significance being that the information gained would aid in the development of therapeutic tools to block malaria transmission.